Multi-center, randomized, double-blind, placebo-controlled study of quetiapine extended-release formulation in Japanese patients with bipolar depression

Abstract

RationaleQuetiapine fumarate is an atypical antipsychotic indicated for various mental disorders, but it has not been studied in Japanese patients with bipolar depression.ObjectivesTo evaluate the efficacy and safety of quetiapine XR (extended release) in Japanese patients with bipolar depression.MethodsIn this multi-center, randomized, double-blind, placebo-controlled, fixed-dose study of 431 Japanese adults with bipolar I or II disorder, efficacy was determined by analyzing the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary end points included MADRS response and remission rates, Hamilton Depression Scale 17-Item (HAM-D17), and Clinical Global Impressions-Bipolar (CGI-BP) scale scores. Safety was determined by monitoring adverse events and clinical assessments.ResultsThis study revealed a statistically significantly greater decrease in MADRS total score after 8 weeks of quetiapine XR 300 mg/day monotherapy compared with placebo (− 12.6 vs. − 10.1; p = 0.034). There were also improvements in MADRS response (44.1 vs. 35.6%) and remission (38.0 vs. 26.6%) rates as well as in HAM-D17 and CGI-BP scale scores compared with placebo. In the subgroup analysis of patients with bipolar I or II disorder, the adjusted mean changes in MADRS total score compared to placebo were − 2.3 and − 2.1, respectively. Adverse events occurred in 149 patients (83.2%) receiving quetiapine XR 300 mg/day and in 81 patients (45.8%) receiving placebo. The most common adverse events were somnolence and thirst, which is consistent with the previously reported safety profile.ConclusionsOnce-daily monotherapy with quetiapine XR is an effective and well-tolerated treatment for bipolar depression in Japanese patients.

Long-term mood/antidepressant effects of quetiapine extended-release formulation: an open-label, non-controlled extension study in Japanese patients with bipolar depression

“…The patient characteristics of the initial 8-week double-blind study were described previously [10]. Of the 179 patients receiving 300 mg quetiapine XR in the previous study, 130 patients transitioned into this extension phase.…”

“…This was a multicenter, open-label, non-controlled extension study to determine the long-term safety and efficacy of quetiapine XR therapy across 98 sites. This study followed on from an 8-week placebo-controlled, double-blind, parallel-group comparative study [10] conducted in Japanese patients with bipolar depression.…”

“…Several clinical studies have demonstrated the efficacy of immediate-release (IR) and extended-release formulations of the atypical antipsychotic quetiapine to reduce depressive symptoms in bipolar disorder [7–9]. We recently showed in an 8-week, placebo-controlled, double-blind, parallel-group comparative study that once-daily monotherapy with 300 mg/day quetiapine XR is an effective and well-tolerated treatment for Japanese patients with bipolar depression [10].…”

The Treatment of Bipolar Depression: Current Status and Future Perspectives

“…In two subsequent RCTs exploring the efficacy and tolerability of quetiapine and active comparators lithium and paroxetine, quetiapine again outperformed placebo in attenuating depressive symptoms while the active comparators did not [9,21]. Placebo-controlled studies of quetiapine extended release (XR) monotherapy have also consistently demonstrated efficacy in bipolar depression [37][38][39]. In terms of relapse prevention, in patients with bipolar I disorder previously stabilised on quetiapine, continued maintenance therapy with quetiapine significantly increases time to recurrence of depressive or manic relapse compared with placebo [40], regardless of any combination with lithium or valproate [41].…”

Quetiapine extended‐release vs olanzapine for Japanese patients with bipolar depression: A Bayesian analysis

“…An 8‐week, double‐blind, randomized, placebo‐controlled phase 3 trial of QUEXR was conducted in Japan . This was a fixed‐dose study comparing QUEXR at 300 mg/d (QUEXR300, n = 179), at 150 mg/d (QUEXR150, n = 74), and placebo (n = 177).…”